Patent Literature 1 discloses tolvaptan represented by Formula (I), which is useful as a vasopressin antagonist with aquaretic activity (i.e., 7-chloro-5-hydroxy-1-[2-methyl-4-(2-methylbenzoylamino)benzoyl]-2,3,4,5-tetrahydro-1H-benzazepine).

Tolvaptan contains a hydroxy-bonded carbon (5-position carbon) as an asymmetric carbon, as shown in Formula (I). Therefore, tolvaptan has a pair of optical isomers (enantiomers) based on the asymmetric carbon. The tolvaptan disclosed in Patent Literature 1 is a racemic compound, i.e., a mixture of equal amounts of the optical isomers (enantiomers) R-(+)-7-chloro-5-hydroxy-1-[2-methyl-4-(2-methylbenzoylamino)benzoyl]-2,3,4,5-tetrahydro-1H-benzazepine (hereafter, may be referred to as R-form) and S-(−)-7-chloro-5-hydroxy-1-[2-methyl-4-(2-methylbenzoylamino)benzoyl]-2,3,4,5-tetrahydro-1H-benzazepine (hereafter, may be referred to as S-form); and has an optical rotation of [α]20D=0°. This racemic tolvaptan is sold as a therapeutic agent against fluid retention in hyponatremia and heart failure.
Processes for producing the optical isomers (R-form and S-form) of tolvaptan are disclosed in Non-patent Literature 1 to 3.
Patent Literature 2 reports that a powdered amorphous solid formulation composition obtained by spray-drying a solution containing tolvaptan and hydroxypropyl cellulose has improved solubility and improved absorbability of tolvaptan from the gastrointestinal tract.
Now, polycystic kidney disease is a hereditary disease in which multiple cysts develop in the kidneys to cause chronic kidney disease (CKD). As the disease progresses, the kidneys develop hypertrophy, leading to end stage renal disease (ESRD), which requires dialysis or transplantation. Vasopressin is believed to promote the growth of cysts, which inhibit the kidney function, in the kidneys of patients with polycystic kidney disease. Tolvaptan, a vasopressin antagonist, is attracting attention as a useful therapeutic agent for polycystic kidney disease.